Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice

The spastic (spa) and oscillator (ot) mouse have naturally occurring mutations in the inhibitory glycine receptor (GlyR) and exhibit severe motor disturbances when exposed to unexpected sensory stimuli. We examined the effects of the spa and ot mutations on GlyR- and GABA(A)R-mediated synaptic transmission in the superficial dorsal horn (SFDH), a spinal cord region where inhibition is important for nociceptive processing. Spontaneous mIPSCs were recorded from visually identified neurones in parasagittal spinal cord slices. Neurones received exclusively GABA(A)R-mediated mIPSCs, exclusively GlyR-mediated mIPSCs or both types of mIPSCs. In control mice (wild-type and spa/+) over 40 % of neurones received both types of mIPSCs, over 30 % received solely GABA(A)R-mediated mIPSCs and the remainder received solely GlyR-mediated mIPSCs. In spa/spa animals, 97 % of the neurones received exclusively GABA(A)ergic or both types of mIPSCs. In ot/ot animals, over 80 % of the neurones received exclusively GABA(A)R-mediated mIPSCs. GlyR-mediated mIPSC amplitude and charge were reduced in spa/spa and ot/ot animals. GABA,Rmediated mIPSC amplitude and charge were elevated in spa/spa but unaltered in ot/ot animals. GlyR- and GABA(A)R-mediated mIPSC decay times were similar for all genotypes, consistent with the mutations altering receptor numbers but not kinetics. These findings suggest the spastic and oscillator mutations, traditionally considered motor disturbances, also disrupt inhibition in a sensory region associated with nociceptive transmission. Furthermore, the spastic mutation results in a compensatory increase in GABA(A)ergic transmission in SFDH neurones, a form of inhibitory synaptic plasticity absent in the oscillator mouse.

Epidemiological and molecular evidence supports the zoonotic transmission of Glardia among humans and dogs living in the same community

Giardia duodenalis isolates recovered from humans and clogs living in the same locality in a remote tea-growing community of northeast India were characterized at 3 different loci; the SSU-rDNA, elongation factor 1-alpha (ef1-alpha) and triose phosphate isomerase (tpi) gene. Phylogenetic analysis of the SSU-rDNA and ef1-alpha genes provided poor genetic resolution of the isolates within various assemblages, stressing the importance of using multiple loci when inferring genotypes to Giardia. Analysis of the tpi gene provided better genetic resolution and placed canine Giardia isolates within the genetic groupings of human isolates (Assemblages A and B). Further evidence for zoonotic transmission was supported by epidemiological data showing a highly significant association between the prevalence of Giardia in humans and presence of it Giardia-positive dog in the same household (odds ratio 3.01, 95%) CI, 1.11, 8.39, P = 0.0000).

Diffuse systemic sclerosis and autoimmune hepatitis: a unique association

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology characterized by continuing hepatocellular necrosis and inflammation that afflicts 100,000 to 200,000 persons in the United States. It is a rare manifestation of systemic sclerosis. Only about nine reports of this association have been previously reported in the literature. Importantly, all cases had the limited clinical form of systemic. The authors describe herein the first report of a patient with diffuse systemic sclerosis who was diagnosed with AIH with positive antimitochondrial antibody and had an excellent response to immunosuppressive drugs. We also briefly review the literature regarding this issue.

Sheep rumen digestion and transmission of weedy Malva parviflora seeds

The effect of sheep digestion and mastication on Malva parviflora L. seed transmission, viability and germination was investigated. Mature M. parviflora seeds were subjected to 2 seed treatments: 'scarified', where the hard seed coat was manually cut to allow inhibition, and 'unscarified', where the hard seed coat was not cut. Seeds were placed directly into the rumen of fistulated sheep and removed at 0, 12, 24, 36 and 48 h of rumen digestion. After 12 h of in sacco exposure to digestion in the rumen, the germination of seeds that were initially scarified dropped from 99.2 to 1.4% and longer exposure periods produced no germinable seeds. In contrast, seeds that were unscarified when placed in the rumen produced over 92% germination regardless of in sacco digestion time, although manual scarification after retrieval was essential to elicit germination. In a second experiment, unscarified seeds (29000) were fed in a single meal to fistulated sheep and feces were collected at regular intervals between 6 and 120 h after feeding. Fecal subsamples were taken to determine number of seeds excreted, seed germination on agar and seed germination from feces. Major seed excretion in the feces commenced after 12 h and continued until 144 h, with peaks between 36 and 72 h after consumption. Although mastication and gut passage killed the majority of unscarified seeds, about 20% were recovered intact and over 90% of these recovered seeds were viable and could, thus, potentially form an extensive seed bank. A few excreted seeds (1%) were able to germinate directly from feces, which increased to a maximum of 10% after subsequent dry summer storage (3 months). Through information gained in this study, there is a potential to utilise livestock in an integrated weed management program for the control of M. parviflora, provided additional measures of weed control are in place such as holding periods (> 7 days) for movement of livestock from weed infested areas.

Prognostic impact of diffuse large B-cell lymphoma subgroups in patients undergoing autologous SCT

A total of 53 patients aged 18-60 years with highintermediate or high-risk diffuse large B-cell lymphoma (DLBCL) were evaluated to analyze the impact of the cell of origin. Of 53 patients, 16 underwent autologous SCT (ASCT) in first remission and the rest received conventional chemotherapy. Immunohistochemistry was evaluated in 47 cases 17 were of germinal center (GC) origin and 30 were of non-GC origin. There was no survival difference between the two groups. Overall survival (OS) and disease-free survival (DFS) at 3 years were 93 and 83%, respectively, for the 14 patients who underwent ASCT. Their DFS was significantly better than that of patients who achieved CR but did not undergo ASCT. We conclude that ASCT is safe and improves the DFS of high-intermediate and high-risk DLBCL, regardless of the cell of origin. This observation should be confirmed in a larger study.

p63 Protein expression in high risk diffuse large B-cell lymphoma

Background: p63 gene is a p53 homologue that encodes proteins with transactivation, DNA-binding and tetramerisation domains. The isoforms TAp63 and TAp73 transactivate p53 target genes and induce apoptosis, whereas the isoforms Delta Np63 and Delta Np73 lack transactivation and might have dominant-negative effects in p53 family members. p63 is expressed in germinal centre lymphocytes and can be related to the development of the lymphoma, but the prognostic significance of its expression in the survival of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. Aims: To determine whether quantitative immunohistochemical (IHC) analysis of p63 protein expression correlates with CD10 antigen, Bcl-6 antigen and IRF4 antigen expression and to determine whether p63 is a surrogate predictor of overall survival in high-intermediate and high risk DLBCL populations. Methods: CD10, Bcl-6 and IRF4 expression were retrospectively evaluated by IHC in 73 samples of high intermediate and high risk DLBCL and were used to divide the lymphomas into subgroups of germinal centre B-celllike (GCB) and activate B-cell-like (ABC) DLBCL. Similarly, p63 expression was evaluated by IHC and the results were compared with subgroups of DLBCL origin and with the survival rates for these patients. Results: p63 was expressed in more than 50% of malignant cells in 11 patients and did not show correlation with subgroups of GCB-like DLBCL or ABC-like DLBCL, but p63(+) patients had better disease-free survival (DFS) than those who were negative (p = 0.01). Conclusions: p63(+) high-intermediate and high risk DLBCL patients have a better DFS than negative cases.

A prognostic score for AIDS-related diffuse large B-cell lymphoma in Brazil

The aim of this study was to evaluate a prognostic score for aids-related lymphoma (ARL). A retrospective study of 104 patients with ARL treated between January 1999 and December 2007 was conducted. Diffuse large B-cell lymphoma (DLBC) was the most observed histological type (79.8%). The median CD4 lymphocyte count at lymphoma diagnosis was 125 cells per microliter. Treatment response could be evaluated in 83 (79.8%) patients, and 38 (45.8%) reached complete remission (CR); overall response rate was 51.8% (95 CI = 38.5-65.1%). After a median follow-up of 48 months, the 4-year overall survival (OS) rate among all patients was 35.8%, with a median survival time of 9.7 months (95% CI = 5.5-13.9 months). The survival risk factors observed in multivariate analysis (previous AIDS and high-intermediate/high international prognostic index (IPI)) were combined to construct a risk score, which divided the whole patient population in three distinct groups as low, intermediate, and high risk. When this score was applied to DLBC patients, a clear distinction in response rates and in OS could be demonstrated. Median disease-free survival (DFS) for patients that achieved CR was not reached, and DFS in 4 years was 83.0%. Our results show that the reduced OS observed could be explained by poor immune status with advanced stage of disease seen in our population of HIV-positive patients. Further studies will be needed to clarify the role of different treatment approaches for ARL in the setting of marked immunosuppression and to identify a group of patients to whom intensive therapy could be performed with a curative intent.

Transmission electron microscopy of a transformation toughened white cast iron

Transmission electron microscopy has been used to study the microstructure of an experimental white cast iran, in which a combination of modified alloy composition and unconventional heat treatment has resulted in a fracture toughness of 40 MPa m(-1/2). Microstructural features of the alloy that contribute to the toughness improvement and hence distinguish it from conventional white irons have been investigated. In the as-cast condition the dendrites are fully austenitic and the eutectic consists of M7C3 carbides and martensite. During heat treatment at 1130 degrees C the austenite is partially destabilized by precipitation of chromium-rich M7C3 carbides. This results in a dendritic microconstituent consisting of bulk retained austenite and secondary carbides which are sheathed with martensite. The martensite sheaths, which contain interlath films of retained austenite, are irregular in shape with some laths extending into the bulk retained austenite. Emphasis has been placed on the morphology, distribution, and stability of the retained austenite and its transformation products in the dendrites. The implications of these findings on the transformation toughening mechanism in this alloy are discussed.

Molecular evidence of horizontal transmission of hepatitis C virus within couples

Hepatitis C virus (HCV) transmission has decreased with the adoption of universal blood donor screening and social policies to reduce the risk of infection in intravenous drug users, but remains a worldwide health problem. The objective of this study was to evaluate the phylogenetic relationships among sequences from different HCV genomic regions from sexual partners of infected patients. Nine couples with a stable relationship and without other risk factors for HCV infection and 42 control patients were selected, and the NS3 and NS5B regions were analysed. Phylogenetic analysis showed that viruses from five of the couples had a common origin, clustering in the same monophyletic group, with bootstrap values greater than 70. For the other couples, monophyletic groups were observed, but without bootstrap support. Thus, using two different viral genome regions, a common source of infection was observed in both members of five couples. These data strongly support HCV transmission within couples.

Modelling congenital transmission of Chagas` disease

The successful elimination of vectorial and transfusional transmission of Chagas` disease from some countries is a result of the reduction of domestic density of the primary vector Triatoma infestans, of almost 100% of coverage in blood serological selection and to the fact that the basic reproductive number of Chagas` disease is very close to one (1.25). Therefore, congenital transmission is currently the only way of acquiring Chagas` Disease in such regions. In this paper we propose a model of congenital transmission of Chagas` disease. Its aim is to provide an estimation of the time period it will take to eliminate this form of transmission in regions where vetorial transmission was reduced to close to zero, like in Brazil. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Diffuse-regressive alterations and apoptosis of myocytes: Possible causes of myocardial dysfunction in HIV-related cardiomyopathy

Objective: To determine the frequency of cardiac alterations in necropsies of AIDS patients in pre-HAART era and better understand the pathogenesis of HIV-related cardiomyopathy. Design: Retrospective study of 94 complete necropsies. Method: Macroscopic, histopathologic (histochemical,immunohistochemical and in situ hybridization techniques) and ultra structural myocardial evaluation (23 cases). Results: Cardiac alterations were observed in 94.4%; 74% showed variable degrees of cardiac dilation not related to known cardiovascular diseases. Eighty-two percent (81.8%) of patients with biventricular dilation showed diffuse-regressive alterations (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules). Myocarditis was diagnosed in 27 cases (28.7%), 16 (59.3%) of known etiology. The ultra structural study has revealed cardiomyocytes alterations (mitochondriosis, loss of myofibrils, increase in the amount of perinuclear-lipofuscin pigment granules) associated to activation signals of capillary-endothelial cells (enhancement of pseudopodia and transcellular channels). Cardiomyocytes` apoptosis was demonstrated at structural level in 10 (43.5%) patients; tumor necrosis factor alpha (TNF alpha) was detected in 17/18 cases. Conclusions: This pioneer study described the association of histopathological and ultra structural findings (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules, mitochondriosis and loss of myofibrils) with different degrees of cardiac-chamber dilation probably representing a spectrum of alterations that would lead to myocardial dysfunction and development of HIV-related cardiomyopathy. Cardiomyocytes` apoptosis observed at ultra structural level and demonstration of TNF alpha associated to described alterations suggest that this cytokine plays an important role in both negative-inotropic effect and capacity to induce apoptosis through death receptor-controlled pathway. (C) 2008 Published by Elsevier Ireland Ltd.

A longitudinal study on the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection in Amazonian Brazil, with special reference to its prevalence and incidence

This was a longitudinal study carried out during a period over 2 years with a cohort of 946 individuals of both sexes, aged 1 year and older, from an endemic area of American visceral leishmaniasis (AVL) in Para State, Brazil. The object was to analyze the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection based principally on the prevalence and incidence. For diagnosis of the infection, the indirect fluorescent antibody test (IFAT) and leishmanin skin test (LST) were performed with amastigote and promastigote antigens of the parasite, respectively. The prevalence by LST (11.2%) was higher (p < 0.0001) than that (3.4%) by IFAT, and the combined prevalence by both tests was 12.6%. The incidences by LST were also higher (p < 0.05) than those by IFAT at 6 (4.7% A- 0.6%), 12 (4.7% A- 2.7%), and 24 months (2.9% A- 0.3%). Moreover, there were no differences (p > 0.05) between the combined incidences by both tests on the same point surveys, 5.2%, 6.3%, and 3.6%. During the study, 12 infected persons showed high IFAT IgG titers with no LST reactions: five children and two adults developed AVL (2,560-10,120), and two children and three adults developed subclinical oligosymptomatic infection (1,280-2,560). The combined tests diagnosed a total of 231 cases of infection leading to an accumulated prevalence of 24.4%.

Urothelial carcinoma transmission via kidney transplantation

Transmission of urothelial carcinoma via solid organ transplant has never been reported in the literature to our knowledge. We report a case of transmission of this tumour to a kidney recipient. The donor was a 37-year-old woman, victim of a subarachnoid haemorrhage. The recipient was a 21-year-old girl, with a history of chronic kidney disease secondary to neurogenic bladder. This fatality has been rarely described in literature, but never with this histological type of cancer. Nowadays, with the expanded criteria for donation, older people are accepted as donor because of the shortage of organs. However, this may increase the likelihood of the number of cancer transmission.

Diffuse plane idiopathic normolipemic xanthoma with hiperesplenism

Diffuse plane normolipemic xanthoma is a rare disease, of a group of clinical syndromes called histiocytoses, characterized by the presence of yellowish or yellow-orange plaques, distributed symmetrically on the cutaneous surface and usually accompanied by xanthelasma. It affects mainly adults and it may cause discrete changes in serum lipids. The case of an 85-year-old female patient who has been showing extensive asymptomatic yellow-orange plaques in the trunk and abdomen for a year is reported. Laboratory tests did not show an increase in serum lipids or the occurrence of reticuloendothelial disorders.

Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers

We investigated the analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in two models of experimental pain in healthy volunteers. Two studies were carried out in parallel in two groups of 26 paid healthy volunteers. The effects of active or sham rTMS (frequency, 10 Hz; intensity, 80% resting motor threshold) applied to the right M1 or DLPFC were compared in a double-blind randomized cross-over design. In the first series of experiments, we analyzed the effects of rTMS on thermal (heat and cold) detection and pain thresholds measured on both hands and the left foot, by standardized quantitative sensory testing methods. In the second series of experiments, we measured the effects of M1 or DLPFC rTMS on the threshold and recruitment curves of the RIII nociceptive reflex evoked by ipsilateral electrical stimulation of the sural nerve and recorded on the biceps femoris of both lower limbs. In both studies, measurements were taken before and up to 60 min after the end of rTMS. Active rTMS of both M1 and DLPFC significantly increased the thermal pain thresholds, measured for both hands and the left foot, this effect being most marked for cold pain. These effects, which lasted at least 1 h after rTMS, were selective because they were not associated with changes in non-painful thermal sensations. By contrast, the second study showed that rTMS of M1 or DLPFC had no significant effect on the threshold or recruitment curve of the nociceptive flexion RIII reflex. Our findings demonstrate that unilateral rTMS of M1 or DLPFC induces diffuse and selective analgesic effects in healthy volunteers. The lack of effect on the RIII reflex suggests that such analgesic effects may not depend on the activation of descending inhibitory systems. (C) 2009 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.